Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer
Authors: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Frank Zimmermann, Giacomo Montagna, Florian Fitzal, Michael Gnant, Thomas Ruhstaller, Simone Muenst, Andreas Mueller, Loïc Lelièvre, Jörg Heil, Michael Knauer, Daniel Egle, Ákos Sávolt, Martin Heidinger, Christian Kurzeder, Daniel R. Zwahlen, Günther Gruber, Markus Ackerknecht, Sherko Kuemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Daniela Hagen, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Christian F. Singer, Sibylle Loibl, Jelena Winkler, Giang Thanh Lam, Mathias K. Fehr, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Nadia Maggi, Alexandra Schulz, Mariacarla Andreozzi, Maite Goldschmidt, Ramon Saccilotto, Pagona Markellou
Journal: JAMA Surgery (2023)

Importance The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)–positive breast cancer (BC) is currently unknown. Objective To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)–positive and Erb-B2 receptor tyrosine kinase 2 ( ERBB2 ; formerly HER2 or HER2/neu )–negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine–DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.